One of the central kproblems of modern biology in the control of cellular growth, both at the cellular level and in the whole organism. The somatomedine or insulin-like growth factors (IGF's) are a group of peptides homologous to insulin which have been shown to have both growth promoting and insulin-like properties in a wide variety of in vitro test systems. Recently, it has also been shown that they can also cause growth of whole organisms in the absence of growth hormone. The somatomedin peptides appear to mediate the growth promoting effects of growth hormone at the tissue level by either endocrine or paracrine mechanisms, or a combination of both. The specific aims of this project are to study the synthesis of IGF mRNA and prohormones, and determine the mechanism of prohormone processing to mature hormone in tissues, to compare the biological action of IGF prohormones and E peptides to IGF-I and IGF-II, to examine the hormonal control of the production of IGF binding proteins, and to examine the role of the specific binding proteins in the biological action of the IGF's The studies will utilize purified and synthetic peptides, high performance liquid chromatography, gel chromatography, ion exchange chromatography, gel electrophoresis, cDNA and mRNS probes, and autoradiography. The tissue culture systems. The long term objectives are to the clarify the hormonal control of the synthesis of the somatomedins, their prohormones and binding proteins, and to clarify the role of the somatomedins, their prohormones and binding proteins in the control of growth at the cellular level, and to extend this knowledge to whole organisms. This work is of importance not only for disorders of human growth in childhood, but in other disease conditions where the cellular conttrol of growth is disturbed, including neoplasia, diabetes, arteriosclerosis and aging.